1. Field of the Invention
The invention relates to a solventless, orally administered pharmaceutical preparation with a delayed active substance release and method for making same, without using any solvents.
2. Brief Description of Related Art
A number of possibilities for making oral slow release drugs are known in the pharmaceutical technology. Different galenic principles are used. The active substance may be modified or diffusion barriers may be erected. In particular the latter principle is very often used in the current practice. The active substance is coated with polymer systems or the drug is bound into matrix systems, from which it is then released. Thereby, mainly organic solvents are used.
Common solvents are used, for example, chlorinated hydrocarbons, in particular methyl chloride, acetone or alcohol.
They will be needed to dissolve the given slow release matrix forming auxiliary agent as well as to coat or bond the remaining auxiliary agents. Furthermore they are used as a wetting agent for granulation purposes.
While hitherto, the reaching of certain goals were in the foreground when developing retarding preparations namely, among others,
maintaining therapeutic plasma concentrations by avoiding active fluctuations over a long period of times; PA1 Avoidance of too high plasma concentration peaks, so as to reduce undesirable effects; PA1 Extend the dosaging interval for obtaining an improved patient compliance. The interest now is directed to be able to make slow release preparations without the use of solvents while obtaining the aforementioned goals.
On account of changed environmental considerations there is now a demand of being able to make drugs without the use of solvents. Official regulations for disposing of the solvents used and in particular the avoidance of toxicological risks of the solvent residue amounts in the drug formulations, for example, chlorinated hydrocarbons, require one not to use solvents when making slow release types of drugs.
Furthermore, in the meantime, it had been shown that within the category of "oral types of drugs," Multiple Unit Dosage Forms have advantages over monolithic form of drugs (Single Units). In particular, from the pharmaceutical point of view, unit dosage forms are preferred over single units. For example, multiple-unit preparations have shorter stomach passage times and permit a rapid and uniform distribution of the defined subunits over the total gastrointestinal tract. Thus local irritations can be avoided due to high drug concentrations. At the same time, the danger of a "dose dumping" is reduced. The fluctuations of the AUC-values and the scatterings of the relevant target dimensions lag time Cmax and tmax are lower.
However, the making of multiple type of slow release drugs in accordance with the hitherto manufacturing methods by using solvents still results in risks for the proper pharmaceutical quality of the preparations. The reproducabilty of a good pharmaceutical quality within one charge (charge homogenity) as well as from charge to charge (charge conformity) is not always assured, (H. Blume, Biopharmaz. Aspekte von Multiple Unit Dosage Forms, 1988).
Although, a whole series of forms of drugs are known for the long time dispensation of active substances, there is still a further need for improved forms of drugs.